A large number of biologically active compounds, including natural products and therapeutics, contain substituted olefins. Chemical synthesis of these motifs can be accomplished by Pd(0)-, Ni(0)-, or Cu(I)- mediated cross-coupling between a nucleophile and a vinyl halide electrophile. A drawback of this chemistry is that substituted vinyl halides are not readily available and typically must be synthesized using methods that have inherently poor atom economy and/or utilize toxic, hazardous materials. An attractive alternative approach would be to perform cross-metathesis between a terminal olefin and a suitable halomethylidene donor. A ruthenium-catalyzed reaction of this type would be expected to have broad functional group tolerance, operate under mild conditions, and offer the potential to affect E/Z selectivity through catalyst control. Despite widespread progress in olefin metathesis in general, cross-metathesis with vinyl halides remains an unsolved problem, and the few reported examples suffer from low catalytic efficiency, a lack of E/Z selectivity, and essentially no reactivity with synthetically useful viny bromides or -iodides. These practical problems are all generally thought to stem from a single fundamental problem, the high thermodynamic stability of the putative [Ru-halomethylidene] intermediate, which renders the catalyst kinetically unreactive and susceptible to decomposition. The goal of this proposal is to develop the first synthetically useful, general protocol for cross- metathesis with vinyl halides through a combined computational, organometallic, and process optimization approach. Specifically, the planned research aims to test the hypothesis that enhanced reactivity can be achieved by using ligand structures that destabilize the [Ru-halomethylidene] ground state through unfavorable dipole-dipole interactions. To this end, computational analysis at the density functional theory (DFT) level will be performed to calculate the free energy profile of productive CM with vinyl halides, as well as that of known decomposition pathways. Next, a series of novel Ru complexes bearing fluorinated biaryl NHC ligands will be prepared, and their chemical behavior will be studied in solution- and solid state. These new catalysts and others will then be tested in vinyl halide CM reactions, with the goal of developing mild and selective protocols to access both (E)- and (Z)-stereoisomers. If successful, this method will have tremendous relevance to pharmaceutical and academic chemistry by streamlining the synthesis of valued vinyl halide intermediates and opening up a new pool of renewable feedstocks as starting materials.